Neural interfaces, which (re)connect the brain with the outside world, are enabling tools for studies of the brain function and also essential elements for a broad range of clinical applications. While intracortical microelectrodes, which can electrically record or stimulate the activity of individual or small populations of neurons, have been known for decades, the discovery that optical signals can be used to interface with neurons is a more recent development. In particular the possibility to activate or mute neurons using photosensitive proteins has opened up new possibilities in the field of neural interfacing. Optogenetic technology is thus generating considerable excitement in neuroscience and biomedical engineering, and has quickly become a widely used toolbox to investigate the brain function and behavior in a broad variety of organisms that ranges from zebrafish to rodents to nonhuman primates.
The majority of optogenetics studies conducted in vivo use optical fibers, which are sometimes guided through an implanted cannula and/or combined with a tungsten microelectrode. In a recent study, Zorzos et al. extended the design concept to three-dimensional microwaveguides, which are capable of delivering light to targets distributed in a 3D pattern throughout the brain. While such optical interfaces have successfully been used in many short-term animal experiments, long-term in vivo studies are only emerging. The possibility to use optogenetic tools under chronic conditions, ideally in freely moving animals and with minimal neuroinflammatory response, is desirable for both fundamental studies and possible clinical applications, but reliable chronic interfaces have proved difficult to realize. A growing body of work gathered in connection with electrophysiological implants suggests that the mechanical mismatch of rigid neural implants and the much softer cortical tissue is a contributing factor to the cell-mediated inflammatory responses, neuronal dieback, and eventual encapsulation of cortical implants. We speculate that the mechanical mismatch of conventional optical fibers and the cortical tissue may cause similar effects in chronic optogenetic applications. One recent approach to alleviate the problems arising from such mechanical mismatch between neural microelectrodes and the cortical tissue is the development of physiologically responsive mechanically adaptive materials, which are sufficiently rigid to permit insertion of small-diameter implants, but which soften considerably upon exposure to emulated physiological conditions. Such adaptive materials can be made by creating nanocomposites consisting of polymers and rigid nanofillers, in which the interactions between the nanofiller particles, and therewith the overall mechanical properties, can be influenced by exposure to water. For example, the tensile storage modulus (B) of nanocomposites based on poly(vinyl alcohol) and cellulose nanocrystals is reduced from ˜14 GPa in the dry state at room temperature to ˜10 MPa upon exposure to simulated physiological conditions. We present here new physiologically responsive mechanically adaptive optical fibers that are useful for optogenetic and other in-vivo applications, because they may reduce inflammatory responses and have other attractive features. For example, they can be bent to adapt desirable shape. No optical fibers that satisfy all of the conditions required are known.
For example, since the introduction of nanocellulose into polymers is normally accompanied by increased light scattering, the aforementioned mechanically adaptive nanocomposites are not well suited as basis for adaptive optical fibers and alternative design approaches are needed.
In view of the above, one problem which the present invention has solved is to develop optical fibers and devices including the same that produce a relatively low neural inflammatory response, wherein the devices can be utilized to stimulate neurons in vivo.
Yet another problem which the present invention has solved is to provide physiologically responsive mechanically adaptive polymer optical fibers exhibiting adequate optical properties, in particular relatively low optical losses.
Still another problem which the invention has solved is to provide optical fibers which have a sufficient rigidity to permit insertion into biological and in particular cortical tissue yet soften to a desired degree upon exposure to conditions encountered in vivo.